Duration of Action/Which Local Anesthetics to Use. Stephan Klessinger, Germany
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1
2 Duration of Action/Which Local Anesthetics to Use Stephan Klessinger, Germany
3 No Disclosures
4 Potency Speed of Onset Duration of Action
5 A Variety of Local Anesthetics Cocaine 1884 Problems: addiction not sterilizable Sigmund Freud Carl Koller
6 Chemical Characteristics Reversible effect Cocaine 1884 Soluble in water Procaine 1905 Sterilizable Procaine: Tissue compatibility slow onset low potency Rapid onset
7 Procaine Structure Cocaine 1884 Procaine 1905 Local Anesthetic ph 5 6 [BH + ]
8 Potency Potency is related to lipid solubility The more lipophilic, the more readily it permeates neuronal membranes greater affinity for sodium channels Cocaine 1884 Procaine 1905 Tetracaine 1930 N H octanol:water partition coefficient Procaine 100 Tetracaine 5822
9 Speed of onset Local Anesthetic ph 5 6 It is the un-ionized form that more readily diffuses across the nerve membrane pka = ph at which a given drug is half ionized and half un-ionized pka approximates physiologic tissue ph means faster onset pka > 9: nearly no effect of LA Low tissue ph (inflammation): less effect of LA Cocaine 1884 Procaine 1905 Tetracaine 1930 Higher concentration speeds the rate of onset octanol:water partition coefficient pka Procaine Tetracaine
10 Classes Esters Cocaine 1884 Allergic reactions Procaine 1905 Cocaine Procaine Tetracaine Benzocaine Tetracaine 1930 Lidocaine 1944 Amides Bupivacaine 1963 Lidocaine Bupivacaine Mepivacaine Ropivacaine i -caine Amides
11 Esters Amides octanol:water partition coefficient Relative Potency pka Onset Type Procaine slow Ester Tetracaine slow Ester Lidocaine fast Amide Bupivacaine slow Amide
12 Duration of Action Protein binding Metabolism Site of injection Channels
13 Duration of Action Protein Binding Protein binding Greater protein binding longer associated with neural membrane Metabolism Site of injection longer duration of action Channels octanol:water partition coefficient Relative Potency pka Onset Protein binding Lidocaine fast 64 % Bupivacaine slow 96 %
14 Duration of Action Metabolism Protein binding Esters: plasma pseudocholinesterase Metabolism Site of injection para-aminobenzoic acid (PABA) allergic reaction more rapidly catabolized, shorter duration of action Channels Amides: metabolism via hepatic P450 enzyme system nearly all metabolism via the liver clearance is highly dependent on hepatic blood flow.
15 Duration of Action Site of injection Protein binding Metabolism Site of Injection Channels The duration of LA action depends on the absorption from from the site of injection dependent on the blood supply The more vascular the location, the more rapidly the agent is absorbed. subcutaneous > intercostal > caudal > epidural > peripheral nerve > intrathecal the use of epinephrine is not recommended for spine procedures
16 Duration of Action Channels Protein binding Metabolism Site of injection used pre-emptively, local anaesthetics act on closed channels. They prevent depolarization used to block ongoing pain, local anesthetics may act on open channels longer duration of action Channels
17 Overview Relative Potenc y Onset Duration of Action Procaine 1 slow Tetracaine 8 slow h Lidocaine 2 fast Bupivacaine 8 slow 2 4 h Ropivacaine 8 slow 2 4 h
18 We Need Two Local Anesthetics Comparative medial branch blocks with: Response: short acting long acting lidocaine bupivacaine concordant discordant discrepant Duration of Action No absolute duration of action for a given local anesthetic Typical mean duration. Duration different for every patient However, in a given patient: short-acting shorter than long-acting Duration measurable in hours, not days
19 Thank you! Forth W, Henschler D, Rummel W, Starke K. Allgemeine und spezielle Pharmakologie und Toxikologie. BI Wissenschaftsverlag. 6. Auflage 1992 Fenton DS, Czervionke LF. Image-Guided Spine Intervention. Saunders, Philadelphia 2002 Baker R, Garg V, Bogduk N. Local Anesthetic Primer for the Interventional Pain Specialist. SIS Bogduk N. Best Practice & Research Clinical Anaesthesiology 2002; 16: Rubin AP, Lawson DIF. Anaesthesia 1968; 23: Watt MJ, Ross DM, Atkinson RS. Anaesthesia 1968; 23: Moore DC, Bridenbaugh LD, et al. Anesthesiology 1970; 32: Moore DC, Bridenbaugh LD, et al. JAMA 1970; 214: Mashimo T, Uchida I et al. Anes Analg 1992; 74: Kim J, Burke SM, et al. World Neurosurg 2016;16: Engel AJ, Bogduk N. Pain Med 2016 Mar 19 [epub ahead of print]
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